While pre-workout supplements may have a reputation for just being caffeinated sugar water, one of the other most well-known, powerful effects of pre-workout supplements (or at least, the good ones) is to increase the “pump” in the gym.
And pre-workouts accomplish this, most commonly, by including supplements that are designed to enhance blood flow via increases in nitric oxide in the blood.
The logic here is simple. More nitric oxide leads to “vasodilation” which is the fancy scientific word for the widening of our blood vessels.
This is like a traffic-jammed one-lane street could suddenly expand and contract into a mega highway with cars moving at highway speeds instead of their slow bumper to bumper. To keep this analogy going, imagine that each one of these cars is carrying vital nutrients (like oxygen) that help our muscles why we train.
(Yes, this expanding highway would be so cool, and shows once again that our infrastructure pales in comparison to what our body is capable of.)
Because of the increase of blood flow and influx in and out of fresh nutrients and waste, improved “pumps” have tons of benefits (in addition to looking and feeling amazing.) They can support recovery, improve the mind-muscle connection, and even help you bang out a few extra reps.
And three of the most well-established nitric oxide boosters are agmatine, arginine, and citrulline. In fact, chemically they’re all related, all like chemical cousins.
But what are the differences between these three common nitric oxide boosters? First, let’s introduce their similarities.
Agmatine, a metabolite of arginine, increases nitric oxide without converting to arginine. It also has a ton of other effects and benefits, as we’ll talk about next.
Arginine also works to increase nitric oxide production directly.
Citrulline converts to arginine, as they’re chemically very similar.
So a simplified framework to think about them in relation to one another is like so:
Citrulline → Arginine → Agmatine
Okay, so which one is better for muscle pumps and more?
We covered agmatine in-depth in this article on agmatine for bodybuilding. The first big difference to understand here is that, unlike arginine and citrulline, agmatine is a neurotransmitter, and has lots of effects on the brain in addition to the rest of the body.
For example, it has been fairly well-established as a pain-relieving substance, a conundrum that we explore in this article on how agmatine interacts with other pain-relievers like kratom. In fact, it has been used in trials to treat neuropathic pain, as well restore sensitivity to drugs, therefore potentially helping combat drug addiction.
Along these lines, it’s also sometimes used as “nootropic” and has many cognitive benefits, although the research here is more limited.
Finally, some studies show that agmatine may improve insulin sensitivity by supporting glucose metabolism. This is an entire dimension to its effects that neither arginine nor citrulline have.
While these benefits may seem great, if you’re not in pain, or currently fighting withdrawal from drug addiction, or you have your own cognition-enhancing nootropic stack that you love, then there’s little reason to go with agmatine. If you don’t want these, then don’t go with agmatine. Go with another option.
That’s especially because agmatine, while very safe, does have a few side effects.
Upset stomach, gastrointestinal distress. The most common of these is GI problems, because agmatine isn’t easy on the stomach.
Tolerance. Second, especially with regards to its pain-relieving effects, you build a tolerance to agmatine.
On the surface, if your goal is muscle pumps, arginine seems like the best decision. After all, arginine itself increases nitric oxide, so why not take it directly?
For decades, this is what bodybuilders have thought too, however research on arginine has barred out surprisingly little evidence for benefits like improved muscle growth and recovery.
That’s because arginine suffers from poor ‘bioavailability’ which means we don’t absorb it well. This means, compared to citrulline, we waste a lot of the arginine we supplement with, even though our body has to go through one fewer metabolic step in order for it to lead to increased pumps.
The other theory behind arginine’s lackluster impact is that our body uses arginine for much more than just nitric oxide production. So when we supplement it, a lot of it will go to other repair areas and to make protein along with other amino acids.
However, on the other hand, this can work in arginine’s favor, as it has been shown to improve wound healing and help speed up recovery from injury. Unlike citrulline and agmatine, arginine is a traditional amino acid, and has lots of benefits for recovery and repair that the others lack.
In that sense, arginine may be viewed as a general recovery supplement that also increases pumps.
Okay, maybe not like Arnold. But the research on citrulline has become clearer and clearer. It gets through the gut much easier than both agmatine and arginine, and then it gets converted into arginine and supports nitric oxide production.
Simply, it seems to raise arginine levels more than arginine itself. As the conclusion of one study said, “Citrulline supplementation is more efficient at increasing arginine availability than arginine supplementation itself in mice.”
The only downside is that you need to take higher doses. But the upside is that without any gut, digestion, or absorption issues, there’s virtually no downside to taking more. And we don’t build a tolerance to it, so you can take relatively high doses (4g-10g) before you workout consistently and it will still give you those pumps.
In general, we often DON’T see a synergistic effect when combining these substances together. In fact, sometimes they nullify their effects.
The mechanisms here are not fully fleshed out yet, but here’s what we know on combining these nitric oxide boosters.
There’s debate about whether these two actually antagonize each other, and from a physiological standpoint, both cases could be made.
Second, they both suffer from digestion, GI, and absorption problems, so it makes more sense right now to stick to one or the other.
These do seem like they could be plausibly combined, and some pre-workouts include both. The situation where this makes sense is if you want the pump boost of citrulline but the repair benefits of arginine. However, in this case, you might as well save your arginine for after your workout.
This has the same mystery as agmatine and arginine. For example, in one study rats given citrulline and agmatine had lower citrulline production than those who just took citrulline, suggesting that they compete for metabolic resources, and this overall hindered nitric oxide production.
If crazy pumps is your goal, go with citrulline.
If repair and recovery is your goal, go with arginine.
If pain relief and cognitive benefits is your goal, go with agmatine.
They’ll all help your muscle pumps, though.